双端氨基聚乙二醇制备工艺优化及表征
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摘要
本实验先采用对甲苯磺酰氯(Ts Cl)与聚乙二醇(PEG)进行酯化反应,制备得到聚乙二醇对甲苯磺酸酯(PEG-OTs)。在一定温度下PEG-OTs与氨水在反应釜中反应制备得到对甲苯磺酸铵盐,并用碱(Na OH)洗得到双端氨基聚乙二醇(AT-PEG),采用正交法对工艺过程优化,在n(PEG)∶n(Ts Cl)为1∶2,氨基化反应时间为6 h,温度为140℃时,双端氨基聚乙二醇得率最高,为54.28%,并采用IR方法对合成产物的结构进行表征。
Polyethylene glycol p-toluene sulfonate( PEG-OTs) was prepared by esterification of toluene sulfonyl chloride( Ts Cl) with polyethylene glycol( PEG6000). At a certain temperature,ammonium p-toluene sulfonic acid was prepared by the reaction of PEG-OTs and ammonia in a reaction kettle,and amino-terminated polyethylene glycol( AT-PEG) was washed by Na OH. The process was optimized by orthogonal method. The highest yield of PEG-bis-amino was obtained at n( PEG) ∶ n( Ts Cl) = 1∶2,6 hours and 140℃,which was 54. 28%,and the structure of the synthesized product was characterized by IR.
Polyethylene glycol p-toluene sulfonate( PEG-OTs) was prepared by esterification of toluene sulfonyl chloride( Ts Cl) with polyethylene glycol( PEG6000). At a certain temperature,ammonium p-toluene sulfonic acid was prepared by the reaction of PEG-OTs and ammonia in a reaction kettle,and amino-terminated polyethylene glycol( AT-PEG) was washed by Na OH. The process was optimized by orthogonal method. The highest yield of PEG-bis-amino was obtained at n( PEG) ∶ n( Ts Cl) = 1∶2,6 hours and 140℃,which was 54. 28%,and the structure of the synthesized product was characterized by IR.
引文
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[7]于宏伟,那海丽,高岩磊,等.双端氨基聚乙二醇的合成[J].化工中间体,2011(9):49-51.
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[9]Chen Yiyan,Baker G L.Synthesis and properties of aba amphiphiles[J].J Org Chem,1999,64(18):6870-6873.
[10]杨保珍,张天民.聚乙二醇修饰超氧化物歧化酶的研究[J].药物生化技术,1998,5(1):12-16.
[11]董炎明.高分子材料实用剖析技术[M].北京:中国石化出版社,1997:80-81.
[12]Kogan T P.The synthesis of substituted methoxypoly(ethyleneglycol)derivatives suitable for selective protein modification[J].Synthetic Communications,1992,22(16):2417-2424.
[2]蒋福升,丁志山,吕圭源.聚乙二醇前药的研究进展[J].中国药学杂志,2007,42(12):881-885.
[3]Claudia Fruijtier-P9lloth.Safety assessment on polyethylene glycols(PEGs)and their derivatives as used in cosmetic products[J].Toxicology,2005(214):1-38.
[4]熊成东,王亚辉,袁龙明,等.聚乙二醇衍生物的合成研究进展[J].高分子通报,2000,39(1):39-45.
[5]王孝杰,孙建平,李效东,等.氨基化单甲氧基聚乙二醇的合成研究[J].精细化工中间体,2006,36(1):40-42.
[6]王琴梅,潘仕荣,张静夏.双端氨基聚乙二醇的制备及表征[J].中国医药杂志,2003,34(10):490-492.
[7]于宏伟,那海丽,高岩磊,等.双端氨基聚乙二醇的合成[J].化工中间体,2011(9):49-51.
[8]Lottner C,Bartk C,Bernhardt G,et al.Soluble tetraarylporphyrin-platintum conjugates cytotoxic and pho-totoxic antitumor agents[J].J Med Chem,2002,45(10):2079-2089.
[9]Chen Yiyan,Baker G L.Synthesis and properties of aba amphiphiles[J].J Org Chem,1999,64(18):6870-6873.
[10]杨保珍,张天民.聚乙二醇修饰超氧化物歧化酶的研究[J].药物生化技术,1998,5(1):12-16.
[11]董炎明.高分子材料实用剖析技术[M].北京:中国石化出版社,1997:80-81.
[12]Kogan T P.The synthesis of substituted methoxypoly(ethyleneglycol)derivatives suitable for selective protein modification[J].Synthetic Communications,1992,22(16):2417-2424.